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目的探讨非洛地平对依那普利及其代谢物依那普利拉在中国健康受试者体内药动学的影响。方法 12例健康受试者(男女各半)采用随机开放二重3×3拉丁方试验设计,受试者在空腹状态下分别口服依那普利片5 mg、非洛地平片5 mg或依那普利片5 mg+非洛地平片5 mg。以高效液相色谱-串联质谱(HPLC-MS/MS)法测定血浆中依那普利及其代谢物依那普利拉的浓度,采用非房室模型法计算药动学参数,用SPSS 18.0软件对主要药动学进行统计学分析。结果单服依那普利片和同服依那普利片+非洛地平片血浆中依那普利的t_(1/2)分别为(1.08±0.59)和(1.17±0.72)h;ρ_(max)分别为(44.27±13.30)和(43.15±8.38)μg·L~(-1);AUC_(0-72h)分别为(84.90±19.50)和(82.70±16.50)μg·h·L~(-1);AUC_(0-∞)分别为(85.80±19.80)和(83.30±16.50)μg·h·L~(-1)。依那普利拉的t_(1/2)分别为(14.73±3.29)和(17.35±5.56)h;ρ_(max)分别为(37.61±15.01)和(34.07±11.78)μg·L~(-1);AUC_(0-72) h分别为(372.60±84.60)和(361.00±90.70)μg·h·L~(-1);AUC_(0-∞)分别为(400.60±84.60)和(361.00±90.70)μg·h·L~(-1)。依那普利及依那普利拉的所有参数均无显著差异(P>0.05)。结论本研究建立的HPLC-MS/MS法快速,灵敏度高,专属性强,测定结果准确,适用于临床试验中依那普利及依那普利拉血药浓度测定;非洛地平对依那普利及其代谢物依那普利拉的药动学无明显影响。
Objective To investigate the effect of felodipine on the pharmacokinetics of enalapril and its metabolite enalaprilat in Chinese healthy subjects. Methods 12 healthy subjects (half male and half female) were randomly assigned to a double-blind 3 × 3 Latin square design. Subjects underwent oral enalapril 5 mg, felodipine 5 mg, Nalaplatin 5 mg + felodipine 5 mg. Pharmacokinetic parameters of enalapril and its metabolite enalaprilat were determined by HPLC-MS / MS with non-compartmental model and SPSS 18.0 The software performs a statistical analysis of the main pharmacokinetics. Results The t_ (1/2) of plasma enalapril in the single-dose enalapril and felodipine + felodipine tablets were (1.08 ± 0.59) and (1.17 ± 0.72) h, respectively; (44.27 ± 13.30) and (43.15 ± 8.38) μg · L -1, respectively; AUC 0-72h were (84.90 ± 19.50) and (82.70 ± 16.50) μg · h · L -1, (-1); AUC_ (0-∞) were (85.80 ± 19.80) and (83.30 ± 16.50) μg · h · L -1, respectively. The values of t_ (1/2) for enalaprilat were (14.73 ± 3.29) and (17.35 ± 5.56) h, respectively, and those for ρ max were (37.61 ± 15.01) and (34.07 ± 11.78) μg · L ~ (- 1). The AUC_ (0-72) h were (372.60 ± 84.60) and (361.00 ± 90.70) μg · h · L -1, and the AUC_ (0 -∞) were (400.60 ± 84.60) and ± 90.70) μg · h · L -1. All parameters of enalapril and enalaprilat did not differ significantly (P> 0.05). Conclusion The HPLC-MS / MS method established in this study is rapid, sensitive, specific and accurate. It is suitable for the determination of enalapril and enalapril in clinical trials. Pulimen and its metabolite enalaprilat pharmacokinetics no significant effect.